Rentsen Badamjav1, Dolgor Sonom2, Yunhao Wu3, Yuanyuan Zhang4, Junping Kou5, Boyang Yu6, Fang Li7. 1. Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Research Center for Traceability and Standardization of TCMs, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, 211198, China. Electronic address: rentsen.ez16@yahoo.com. 2. Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Research Center for Traceability and Standardization of TCMs, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, 211198, China. Electronic address: dolgor.daoge@yahoo.com. 3. Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Research Center for Traceability and Standardization of TCMs, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, 211198, China. Electronic address: elvis789@163.com. 4. Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Research Center for Traceability and Standardization of TCMs, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, 211198, China. Electronic address: cpuzhang27@163.com. 5. Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Research Center for Traceability and Standardization of TCMs, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, 211198, China. Electronic address: junpingkou@cpu.edu.cn. 6. Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Research Center for Traceability and Standardization of TCMs, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, 211198, China. Electronic address: boyangyu59@163.com. 7. Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Research Center for Traceability and Standardization of TCMs, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, 211198, China. Electronic address: lifangcpu@163.com.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Thalictrum minus L., a Mongolian folk medicinal plant, was applied for the treatment of bacterial and fungal infection, tuberculosis and lung inflammation. AIM OF THE STUDY: The present work aims to elucidate the protective effects of Thalictrum minus L.(TML) against lipopolysaccharide (LPS)-induced acute lung injury and the underlying mechanisms. METHODS: The mice model of acute lung injury was induced by LPS via endotracheal drip, and TML (10, 20, 40 mg/kg) were administered orally 1 h prior to LPS. The efficacy and molecular mechanisms in the presence or absence of TML were investigated. RESULTS: We demonstrated that treatment with TML aqueous extract protected the mice from acute lung injury induced by LPS administration. TML significantly inhibited weight loss in mice, decreased the lung wet to dry weight (W/D) ratios and attenuated lung histopathological changes, such as infiltration of inflammatory cells and coagulation, pulmonary edema. Furthermore, we found that TML markedly reduced the LPS-induced inflammatory cytokines including tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), decreased nitric oxide (NO), and increased superoxide dismutase (SOD) in bronchoalveolar lavage fluid (BALF), and effectively ameliorated LPS-induced increased total protein, leukocyte and macrophages in BALF. In addition, TML pronouncedly suppressed the activation of the MAPKs p38-NLRP3/caspase-1 and COX2, increased the expression of p-AMPK-Nrf2, and suppressed the expression of KEAP, apoptotic-related protein as well as autophagy. CONCLUSIONS: These results suggested that TML ameliorated LPS-induced acute lung injury by inhibiting the release of inflammatory cytokines and reducing oxidative damage associated with the MAPKs p38-NLRP3/caspase-1 and COX2 signaling pathways, AMPK-Nrf2/KEAP signaling pathways, as well as apoptosis and autophagy.
ETHNOPHARMACOLOGICAL RELEVANCE: Thalictrum minus L., a Mongolian folk medicinal plant, was applied for the treatment of bacterial and fungal infection, tuberculosis and lung inflammation. AIM OF THE STUDY: The present work aims to elucidate the protective effects of Thalictrum minus L.(TML) against lipopolysaccharide (LPS)-induced acute lung injury and the underlying mechanisms. METHODS: The mice model of acute lung injury was induced by LPS via endotracheal drip, and TML (10, 20, 40 mg/kg) were administered orally 1 h prior to LPS. The efficacy and molecular mechanisms in the presence or absence of TML were investigated. RESULTS: We demonstrated that treatment with TML aqueous extract protected the mice from acute lung injury induced by LPS administration. TML significantly inhibited weight loss in mice, decreased the lung wet to dry weight (W/D) ratios and attenuated lung histopathological changes, such as infiltration of inflammatory cells and coagulation, pulmonary edema. Furthermore, we found that TML markedly reduced the LPS-induced inflammatory cytokines including tumornecrosis factor-α (TNF-α) and interleukin-1β (IL-1β), decreased nitric oxide (NO), and increased superoxide dismutase (SOD) in bronchoalveolar lavage fluid (BALF), and effectively ameliorated LPS-induced increased total protein, leukocyte and macrophages in BALF. In addition, TML pronouncedly suppressed the activation of the MAPKs p38-NLRP3/caspase-1 and COX2, increased the expression of p-AMPK-Nrf2, and suppressed the expression of KEAP, apoptotic-related protein as well as autophagy. CONCLUSIONS: These results suggested that TML ameliorated LPS-induced acute lung injury by inhibiting the release of inflammatory cytokines and reducing oxidative damage associated with the MAPKs p38-NLRP3/caspase-1 and COX2 signaling pathways, AMPK-Nrf2/KEAP signaling pathways, as well as apoptosis and autophagy.